Parsing events during MS3 experiments

• US 9,768,002 B2
• Filed: 04/13/2016
• Issued: 09/19/2017
• Est. Priority Date: 12/20/2012
• Status: Active Grant

• Current Assignee: DH Technologies Development Pte. Ltd. (Danaher Corporation)
• Original Assignee: DH Technologies Development Pte. Ltd. (Danaher Corporation)
• Inventors: Campbell, John Lawrence
• Primary Examiner(s): STOFFA, WYATT A
• Application Number:
  US15/098,199
• Publication Number:
  US 20160233064A1
• Time in Patent Office: 524 Days
• CPC Class Codes: H01J 49/0031 Step by step routines describing the use of the apparatus H01J49/0081 takes precedence
• CPC Class Codes: H01J 49/005 by collision with gas, e.g. by introducing gas or by accelerating ions with an electric field

Abstract

Systems and methods are provided for reducing the time period of a CID event of an MS³ experiment and making the overall fragmentation event more generic. A CID event of an MS³ experiment performed on a sample by a mass spectrometer is divided into two time periods using a processor. At the beginning of a first time period of the CID event, the mass spectrometer is instructed to both open a pulse valve in order to pulse a collision gas and apply a first CID voltage. At the beginning of a second time period of the CID event, the mass spectrometer is instructed to both close the pulse valve and apply a second CID voltage. The mass spectrometer is pumped down during the second time period. The overlap in time of the pump down and CID reduces the overall time period of the CID event.

Claims

1. A system for segmenting a collision-induced dissociation (CID) event of a mass spectrometry/mass spectrometry/mass spectrometry (MS³) experiment, comprising:

a mass spectrometer that performs an MS³ experiment on a sample;

a processor in communication with the mass spectrometer that

divides a CID event of the MS³ experiment into two time periods,

at the beginning of a first time period of the CID event, instructs the mass spectrometer to both open a pulse valve in order to pulse a collision gas and apply a first CID voltage, and

at the beginning of a second time period of the CID event, instructs the mass spectrometer to both close the pulse valve and apply a second CID voltage, wherein the mass spectrometer is pumped down during the second time period allowing pump down and CID to overlap in time

receives a plurality of second generation fragmentation spectra from the MS³ experiment, and

selects the most intense second generation fragment ions with the lowest noise from the plurality of second generation fragmentation spectra.

2. The system of claim 1, wherein the first CID voltage and the second CID voltage are the same CID voltage.

3. The system of claim 1, wherein the second generation fragmentation ions are selected post-acquisition.

4. The system of claim 1, wherein the first CID voltage and the second CID voltage are different CID voltages and the difference in voltage between the first CID voltage and the second CID voltage causes a step in collision energy across the CID event.

5. The system of claim 1, wherein the first time period and the second time period have different lengths.

6. The system of claim 1, wherein the processor selects the second generation fragment ions that have an intensity above a threshold intensity level and a signal-to-noise ratio (S/N) above a threshold S/N level to identify a compound.

7. A method for segmenting a collision-induced dissociation (CID) event of a mass spectrometry/mass spectrometry/mass spectrometry (MS³) experiment, comprising:

dividing a CID event of an MS³ experiment performed on a sample by a mass spectrometer into two time periods using a processor;

at the beginning of a first time period of the CID event, instructing the mass spectrometer to both open a pulse valve in order to pulse a collision gas and apply a first CID voltage using the processor;

at the beginning of a second time period of the CID event, instructing the mass spectrometer to both close the pulse valve and apply a second CID voltage using the processor, wherein the mass spectrometer is pumped down during the second time period allowing pump down and CID to overlap in time;

receiving a plurality of second generation fragmentation spectra from the MS³ experiment using the processor; and

selecting the most intense second generation fragment ions with the lowest noise from the plurality of second generation fragmentation spectra using the processor.

8. The method of claim 7, wherein the first CID voltage and the second CID voltage are the same CID voltage.

9. The method of claim 7, wherein the second generation fragmentation ions are selected post-acquisition.

10. The method of claim 7, wherein the first CID voltage and the second CID voltage are different CID voltages and the difference in voltage between the first CID voltage and the second CID voltage causes a step in collision energy across the CID event.

11. The method of claim 7, wherein the first time period and the second time period have different lengths.

12. The method of claim 7, wherein the second generation fragment ions that have an intensity above a threshold intensity level and a signal-to-noise ratio (S/N) above a threshold S/N level are selected to identify a compound.

13. A computer program product, comprising a non-transitory and tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for segmenting a collision-induced dissociation (CID) event of a mass spectrometry/mass spectrometry/mass spectrometry (MS³) experiment, the method comprising:

providing a system, wherein the system comprises one or more distinct software modules, and wherein the distinct software modules comprise an analysis module and a control module;

dividing a CID event of an MS³ experiment performed on a sample by a mass spectrometer into two time periods using the analysis module;

at the beginning of a first time period of the CID event, instructing the mass spectrometer to both open a pulse valve in order to pulse a collision gas and apply a first CID voltage using the control module;

at the beginning of a second time period of the CID event, instructing the mass spectrometer to both close the pulse valve and apply a second CID voltage using the control module;

wherein the mass spectrometer is pumped down during the second time period allowing pump down and CID to overlap in time;

receiving a plurality of second generation fragmentation spectra from the MS³ experiment using the analysis module; and

selecting the most intense second generation fragment ions with the lowest noise from the plurality of second generation fragmentation spectra using the analysis module.

14. The computer program product of claim 13, wherein the first CID voltage and the second CID voltage are the same CID voltage.

15. The computer program product of claim 13, wherein the second generation fragmentation ions are selected post-acquisition.

16. The computer program product of claim 13, wherein the first CID voltage and the second CID voltage are different CID voltages and the difference in voltage between the first CID voltage and the second CID voltage causes a step in collision energy across the CID event.

17. The computer program product of claim 13, wherein the first time period and the second time period have different lengths.

18. The computer program product of claim 13, wherein the second generation fragment ions that have an intensity above a threshold intensity level and a signal-to-noise ratio (S/N) above a threshold S/N level are selected to identify a compound.